Abstract

Although beta-amyloid, anxiety and depression have linked cross-sectionally to reduced memory function in healthy older adults without dementia, prospective data evaluating these associations are lacking. Using data an observational cohort study of 178 healthy older adults without dementia followed for 3 years, we found that anxiety symptoms significantly moderated the relationship between beta-amyloid level and decline in verbal (Cohen’s d = 0.65) and episodic (Cohen’s d = 0.38) memory. Anxiety symptoms were additionally linked to greater decline in executive function, irrespective of beta-amyloid and other risk factors. These findings suggest that interventions to mitigate anxiety symptoms may help delay memory decline in otherwise healthy older adults with elevated beta-amyloid. Beta-amyloid accumulates incrementally with age and is abnormally elevated in the majority of individuals who meet criteria for mild cognitive impairment or Alzheimer’s disease.1 Abnormal levels of beta-amyloid are also seen in about 30% of healthy older adults without dementia2 and are associated with clinically significant decline in episodic memory over 18-36 months.3 Anxiety and depression are also linked to increased beta-amyloid in healthy older adults without dementia, as well as in adults with mild cognitive impairment or Alzheimer’s disease,4,5 and are known to deleteriously affect episodic memory and related cognitive functions, such as attention and executive function.6,7 Taken together, these observations suggest that anxiety and depression may contribute to beta-amyloid-related decline in episodic memory and related cognitive domains in otherwise healthy older adults. Given that anxiety and depression are amenable to treatment, their identification as determinants or moderators of beta-amyloid-related cognitive decline in healthy older people is important for managing preclinical and prodromal phases of Alzheimer’s disease prior to the availability of anti-amyloid therapies. We evaluated whether elevated anxiety and depressive symptoms moderated the effect of elevated beta-amyloid on cognitive decline in one of the largest cohorts of healthy older adults without dementia who have undergone assessment with 11C-Pittsburgh Compound B (PiB) and whose clinical status was followed prospectively over 3 years. We hypothesised that elevated anxiety and depressive symptoms at baseline would be associated with increased memory decline over the 3-year period of assessment, and that this effect would be independent of traditional risk factors for cognitive decline (such as age, education, IQ and apolipoprotein E (APOE) genotype).